Long-term fluoxetine, but not desipramine, inhibits the ACTH and oxytocin responses to the 5-HT1A agonist, 8-OH-DPAT, in male rats.

The present studies determined whether serotonin 5-HT1A receptor-mediated function is modified by chronic exposure to antidepressants. Hormone responses to the 5-HT1A agonist, 8-OH-DPAT, were evaluated after long-term exposure to two antidepressants, the 5-HT uptake blocker, fluoxetine, and the norepinephrine uptake blocker, desipramine (DMI). In addition, the density and affinity of 5-HT1A receptors in the hypothalamus and cerebral cortex were measured. Male rats received fluoxetine (10 mg/kg i.p.), DMI (5 mg/kg i.p.) or saline injections once daily for 21 days. 8-OH-DPAT (0-500 micrograms/kg s.c.) was administered 18 h after the final antidepressant injection and 15 min before sacrifice. 8-OH-DPAT significantly increased plasma ACTH, corticosterone, oxytocin and prolactin, but not renin or vasopressin concentrations. Chronic injections of fluoxetine inhibited the ACTH, corticosterone and oxytocin responses to 8-OH-DPAT, suggesting reduced 5-HT1A receptor function. In contrast, chronic DMI did not alter the hormone responses to 8-OH-DPAT. The density and affinity of 5-HT1A receptors in the frontal cortex or hypothalamus were not altered by either fluoxetine or DMI. To verify that the observed effects require prolonged exposure to fluoxetine, rats received a single injection of fluoxetine (10 mg/kg, i.p.), 3 h before 8-OH-DPAT (0-500 micrograms/kg s.c.). Acute fluoxetine did not reduce any of the hormone responses to 8-OH-DPAT. In conclusion, the results suggest that chronic, but not acute, exposure to fluoxetine decreases 5-HT1A receptor function. This effect is not seen in rats chronically exposed to DMI.(ABSTRACT TRUNCATED AT 250 WORDS)